Preferential upregulation of interferon-α subtype 2 expression in HIV-1 patients

Humans tailor virus-specific immune responses through modulated expression of 12 different interferon (IFN)-α subtypes. However, exacerbated expression of certain IFN-α subtypes causes immunopathology in the context of autoimmune conditions and chronic viral infections. We showed that progression to AIDS is associated with elevated expression of IFN-α in unstimulated peripheral blood mononuclear cells. Here, we sought to determine whether distinct IFN-α subtypes are involved in this phenomenon. We used quantitative RT-PCR to assess expression levels of 12 IFN-α subtypes in peripheral blood mononuclear cells from normal donors and HIV-1 patients at CDC stage A and stage C of the disease. Three patterns of IFN-α subtype expression emerged. First, IFN-α2 and IFN-α6 mRNA levels were elevated in both patient groups. Second, IFN-α1/13, IFN-α8, IFN-α14, IFN-α16, IFN-α17, and IFN-α21 were upregulated in stage C but not stage A patients. Third, expression levels of IFN-α4, IFN-α5, IFN-α7, and IFN-α10 did not change among the three groups of volunteers. Among all other subtypes, IFN-α2 was preferentially upregulated, showing >60-fold higher levels in stage A and >400-fold in stage C patients compared with controls, which correlated with declining CD4 counts. Our results demonstrate that distinct IFN-α subtypes are sequentially activated during HIV-1 infection, which may be predictive of disease progression.